In the fields of orthopedics (e.g., reconstructive, trauma, spine, and dentistry), effective repair of bone defects, which may have been caused by disease, injury, wounds, or surgery, has long been a goal. A number of materials and compositions have been considered, evaluated, or used. Beyond their ability to promote bone growth, the biological, physical, and mechanical properties of the materials and compositions are factors, among others, affecting their suitability and performance in various applications.
Bone grafting has been commonly used to augment healing in treating a variety of musculoskeletal disorders. Grafting techniques in this field have been practiced for over 100 years and include procedures employing autograft, allograft and xenograft materials. Autologous cancellous bone is considered the standard against which other treatments are evaluated. Autograft cancellous bone is non-immunogenic and has all the appropriate structural and functional characteristics appropriate for the particular recipient. Autograft cancellous bone provides both a natural tissue scaffold and osteoinductive growth factors and may also contain osteogenic components (e.g., mesenchymal stem cells) if obtained with bone marrow. Autologous cancellous bone, however, is not acceptable or otherwise available for all patients. Autograft sources, as well as allograft sources, are relatively limited and may be expensive or painful to obtain. These and other limitations of autografts and allografts have resulted in alternative compositions being pursued as graft substitutes to fill defects (e.g., voids) in bone. Numerous bone graft substitutes having osteoinductive and/or osteoconductive properties have been explored and include, but are not limited to, products containing hydroxyapatites, tricalcium phosphates, aliphatic polyesters (poly(lactic) acids (PLA), poly(glycolic)acids (PGA), and polycaprolactone (PCL)), polyhydroxybutyrate (PHB), cancellous bone allografts, human fibrin, plaster of Paris, apatite, wollastonite (calcium silicate), bioactive glasses, ceramics, titanium, devitalized bone matrix, non-collagenous proteins, collagen, and autolyzed antigen extracted allogenic bone.
Demineralized bone, in the form of scaffold, granules, particulate, and/or powder, has been used in certain bone graft substitutes due to its osteoinductive properties. Osteoinductive components induce bone formation by stimulating stem cells and osteoprogenitor cells to undergo the osteogenic differentiation pathway. In the 1960's, demineralized bone was observed to induce the formation of new cartilage and bone when implanted in ectopic sites (Urist, 1965, Science 150:893-899). Demineralized bone can be prepared by grinding a bone, demineralizing it with an acid solution, washing with water or a phosphate buffered solution, washing with ethanol and drying it. Demineralized bone may be obtained from a source such as a commercial bone or tissue bank (e.g., AlloSource, Denver Colo.).